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Providing surgical margin information during breast cancer surgery is crucial for the success of the procedure. The margin is defined as the distance from the tumor to the cut surface of the resection specimen. The consensus among surgeons and radiation oncologists is that there should be no tumor left within 1 to maximum 2 mm from the surface of the surgical specimen. If a positive margin remains, there is substantial risk for tumor recurrence, which may also result in potentially reduced cosmesis and eventual need for mastectomy. In this paper we report a novel multimodal optical imaging instrument based on combined high-resolution confocal microscopy-optical coherence tomography imaging for assessing the presence of potential positive margins on surgical specimens. Since rapid specimen analysis is critical during surgery, this instrument also includes a fluorescence imaging channel to enable rapid identification of the areas of the specimen that have potential positive margins. This is possible by specimen incubation with a cancer specific agent prior to imaging. In this study we used a quenched contrast agent, which is activated by cancer specific enzymes, such as urokinase plasminogen activators (uPA). Using this agent or a similar one, one may limit the use of high-resolution optical imaging to only fluorescence-highlighted areas for visualizing tissue morphology at the sub-cellular scale and confirming or ruling out cancer presence. Preliminary evaluation of this technology was performed on 20 surgical specimens and testing of the optical imaging findings was performed against histopathology. The combination of the three imaging modes allowed for high correlation between optical image analysis and histological ground-truth. The initial results are encouraging, showing instrument capability to assess margins on clinical specimens with a positive predictive value of 1.0 and a negative predictive value of 0.83.

We present a novel technology based on a high sensitivity/specificity cancer targeting agent and of a novel fluorescence-guided microscopy (FGM) scheme for intraoperative assessment of surgical margins in breast cancer patients. Cancer cells are targeted using an optically silent peptide substrate coupled to a near infrared (NIR) fluorochrome that is cleaved by highly mediated breast cancer enzymes, like urokinase-type plasminogen activator (uPA), to become highly fluorescent when excited by a NIR laser beam. A FGM instrument is used to localize cancer-suspect areas on the lumpectomy specimen and visualize tissue morphology at the sub-cellular scale, such that a trained pathologist can read these images in real-time and confirm or rule-out cancer presence. The proposed technology will enable efficient assessment of surgical specimens during surgery, when it is mostly needed, and therefore help the clinician to determine if additional tissue excision is needed or not. The preliminary testing of this technology on breast surgical specimens will be discussed.

Integrating logical constraints into optimal control problems is not an easy task. In fact, optimal control problems are usually continuous while logical constraints are naturally expressed by integer (binary) variables. In this article we are interested is a particular form of an LQR optimal control problem: the energy (control L2 norm) is to be minimized, system dynamic is linear and logical constraints on the control use are to be fulfilled. Even if the starting continuous problem is not a complicated one, difficulties arise when integrating the additional logical constraints. First, we will present two different ways of modeling the problem, both of them leading us to Mixed Integer Problems. Furthermore, algorithms (Generalized Outer Approximation, Benders Decomposition and Branch and Cut) are applied on each model and results analyzed. We also present a Benders Decomposition algorithm variant that is adapted to our problem (taking into account its particular form) and we will conclude by looking at the optimal solutions obtained in an interesting physical example: the harmonic spring.

We demonstrate the feasibility of a surgery guidance approach based on fluorescence-guided optical coherence tomography (OCT) imaging. Surgical margins are assessed for cancer presence using automated analysis of OCT images, only on areas indicated by fluorescence imaging as being cancer suspicious.

The synthesis and structure-activity relationships against the C3a receptor of a series of substituted aminopiperidine derivatives are reported. DMPK properties and functional activities of selected compounds are described. The compounds obtained are the first non-arginine ligands of C3aR.

The synthesis and in vitro binding of several new arginine-containing C3aR ligands are reported. DMPK properties and functional activities of selected compounds have been evaluated. One compound is shown to be active in an in vivo model of airway inflammation after aerosol administration.